In the era of increased antibiotic resistance, targeting enzymes involved in bacterial communication (quorum sensing) represents a new strategy to fight bacterial infections. LsrK is a kinase responsible for the phosphorylation of autoinducer‐2, a signaling molecule involved in quorum sensing. Inhibiting LsrK would lead to quorum sensing inactivation and interfere with the pathogenesis. In this study, we built the first LsrK 3D model and performed virtual screening of a locally available database. Selected compounds were tested against LsrK, and the analogue search conducted based on the positive hits led to the identification of low‐micromolar LsrK inhibitors. These results prove the utility of the model and provide the first class of LsrK inhibitors to be further optimized as antivirulence agents.

中文翻译：

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LsrK激酶抑制剂基于结构的虚拟筛选，以靶向群体感应。

在抗生素耐药性增加的时代，与细菌交流（群体感应）有关的靶向酶代表了对抗细菌感染的新策略。LsrK是负责自动诱导子2磷酸化的激酶，autoinducer-2是参与群体感应的信号分子。抑制LsrK将导致群体感应失活并干扰发病机理。在这项研究中，我们建立了第一个LsrK 3D模型，并对本地可用数据库进行了虚拟筛选。对选定的化合物进行了针对LsrK的测试，并基于阳性结果进行了类似搜索，从而鉴定出了低微摩尔LsrK抑制剂。这些结果证明了该模型的实用性，并提供了第一类LsrK抑制剂，可以进一步优化其作为抗毒剂。